Radiation and radiochemically sterilized fiber-reinforced, composite urinogenital stents

ABSTRACT

A radiation and radiochemically sterilized, multi-component, fiber-reinforced composite, absorbable/disintegratable urinogenital stent, such as an endoureteral stent, with radiomodulated residence time in the biological site of 1 to 10 weeks depending on the high energy radiation dose used for sterilization.

This application is a continuation-in-part of U.S. Ser. No. 11/346,117,filed Feb. 2, 2006, which is a continuation-in-part application of U.S.Ser. No. 11/204,822 filed Aug. 16, 2005, which claims the benefit ofprior provisional application U.S. Ser. No. 60/650,240 filed Feb. 4,2005.

FIELD OF THE INVENTION

This invention relates to patient-customized, non-migrating,fiber-reinforced, composite absorbable/disintegratable urinogenitalstent that is radiochemically sterilized with about 3 to 15 kGy andradiation sterilized with 25 to 40 kGy of high-energy radiation tomodulate its residence time in a typical urinogenital conduit such as aureter in order to maintain optimum ureteral patency for predeterminedperiods of time between 1 and 10 weeks. At the conclusion of thespecific predetermined period, the stent is expected to have practicallyno physical presence in the ureter that may interfere with pertinentbiological functions.

BACKGROUND OF THE INVENTION

Most pertinent to this application are a number of aspects of the priorapplication of U.S. Ser. No. 11/346,117 which dealt with (1) anabsorbable/disintegratable, multicomponent, non-migrating, endoureteralstent which is a tubular construct of a fiber-reinforced, elastomeric,tubular film designed with at least one position retaining end which canbe in the form of a flexible, reversible loop or pigtail; and (2)fiber-reinforced stent wherein the fiber reinforcement is a combinationof radiopaque monofilament coil made of an absorbable, segmented,polyaxial copolyester with barium sulfate microparticles dispersedtherein and a weft-knitted mesh made of multifilament yarn derived froman absorbable, segmented, polyaxial copolyester. However, the priorapplication was silent on (1) relating the claimed composition of theconstruct component to definite residence time in a conduit such as theureter; (2) addressing how to facilitate the insertion of the stent intoa moist conduit tract, in part with the aid of a pusher and guide wire,without compromising the physical integrity of the stent; and (3)dealing with how to package and sterilize the stent and itscomplementary components, should ethylene oxide, the standardsterilization method for absorbable devices, is deemed less than optimumfor use. The silence of the prior application on these clinicallyimportant aspects of a useful stent provided an incentive to pursue thestudy subject of this invention. Accordingly, this invention deals witha fiber-reinforced composite, absorbable/disintegratable, urinogenitalstent that is radiochemically sterilized or radiation sterilized usingthe proper dose to modulate its residence time in a specificurinogenital conduit, such as a ureter, for a predetermined period oftime ranging between 1 and 10 weeks.

SUMMARY OF THE INVENTION

A general aspect of the invention deals with a multi-componentabsorbable/ disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit, the stent comprising afirst component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles, wherein theurinogenital conduit is selected from the group consisting of ureters,urethras, vas deferens, uterine tubes, fallopian tubes and ejaculatoryducts, and wherein the stent is in the form of a tube having a maincentral body and at least one position-retaining end comprising aflexible extension of the main central body, and having a loop shapewith an open end parallel to the axis of the main central body afterinsertion in the urinogenital conduit wherein the loop can be madeco-linear with the aid of an applicator. Additionally, the stent is inthe form of an endoureteral stent having a diameter that is less thanthat of the urinogenital conduit and the matrix component comprises anabsorbable, high molecular weight, low-crystallinity, segmentedpolyaxial copolyester exhibiting an inherent viscosity of from about 0.5to about 2.0 dL/g and heat of fusion (ΔH_(f)) of from about 2 to about30 J/g and derived from l-lactide and at least one additional monomerselected from the group consisting of glycolide, trimethylene carbonate,ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione.

A key aspect of this invention deals with a multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit, the stent comprising afirst component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles, wherein thematrix comprises an absorbable, segmented, polyaxial copolyester and ahigh molecular weight, hydrophilic polymeric additive having a molecularweight of about 1 to about70 kDa, the additive selected from the groupconsisting of polyethylene glycol, and polyethylene glycol end-graftedwith at least one monomer selected from the group consisting ofl-lactide, glycolide, trimethylene carbonate, ε-caprolactone,p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione, and wherein thematrix comprises an absorbable polyether-ester comprising an aliphaticpolyether glycol end-grafted with at least one monomer selected from thegroup consisting of l-lactide, glycolide, trimethylene carbonate,ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-one and a morpholinedioneand having an inherent viscosity of from about 0.6 to about 1.8 dL/g andan overall heat of fusion (ΔH_(f)) of from about 5 to about 30 J/g, andfurther wherein the load-bearing radiopaque central reinforcing coilcomprises a hybrid monofilament consisting of from about 30 to about 60weight percent of barium sulfate microparticles dispersed in acrystalline high molecular segmented polyaxial copolyester exhibiting aninherent viscosity of from about 0.6 to about 2.0 dL/g and a heat offusion (ΔH_(f)) of from about 20 to about 80 J/g, the copolyesterderived from glycolide and at least one additional monomer selected fromthe group consisting of l-lactide, trimethylene carbonate,ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione.

Another key aspect of this invention deals with multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit, the stent comprising afirst component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles, wherein theabsorbable multifilament yarn of the knitted mesh comprises acrystalline, high molecular weight segmented polyaxial copolyesterexhibiting an inherent viscosity of from about 0.6 to about 2.3 dL/g anda heat of fusion (ΔH_(f)) of from about 30 to about 90 J/g, thecopolyester derived from glycolide and at least one additional cyclicmonomer of l-lactide, trimethylene carbonate, ε-caprolactone,p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione, and wherein thestent is packaged in a dry, hermetically sealed foil pack and isirradiated with from about 3 to about 35 kGy of high energy radiation.Alternatively, wherein the stent is packaged in a dry, hermeticallysealed foil pack and is irradiated with from about 30 to about 40 kGy ofgamma rays or electron beam radiation.

A technologically important aspect of this invention deals with amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit, the stentcomprising a first component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles and whereinthe stent is packaged in a dry, hermetically sealed foil pack containinga formaldehyde-generating packet, and is irradiated with from about 3 toabout 15 kGy of gamma rays or electron beam radiation.

A second general aspect of this invention deals with a multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit, the stent comprising afirst component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, at least threeabsorbable strands overlying the coil and extending along thelongitudinal axis of the stent, the strands comprising a copolyesterderived from at least one monomer selected from the group consisting ofl-lactide, glycolide, trimethylene carbonate, ε-caprolactone,p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione, wherein the stentexhibits a one- to ten-week, radiomodulated absorption/disintegrationand strength retention profiles and wherein the absorbable strands areselected from the group consisting of monofilament yarn having adiameter between about 20 and about 150 microns, a 20-filament, 60 to100 denier yarn, and a braided multifilament yarn having a diameter offrom about 0.02 to about 0.2 mm.

A clinically important aspect of this invention deals with amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit, the stentcomprising a first component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles wherein saidstent comprises at least one bioactive agent selected from the groupconsisting of antimicrobial, antiviral, antineoplastic, anti-anesthetic,anti-inflammatory, analgesic, and cell-growth promoting agents andwherein the at least one bioactive agent comprises an antimicrobialagent and wherein the antimicrobial agent comprises an antibacterialagent selected from the group consisting of triclosan, clindamycin,mitomycin, doxycycline, and metronidazole and further wherein the atleast one bioactive agent comprises an antimicrobial agent and whereinthe antimicrobial agent comprises antifungal agent selected from thegroup consisting of miconazole, fluconazole, and ketoconazole.

Another clinically important aspect of this invention deals with amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit, the stentcomprising a first component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles wherein saidstent comprises at least one bioactive agent selected from the groupconsisting of antimicrobial, antiviral, antineoplastic, anti-anesthetic,anti-inflammatory, analgesic, and cell-growth promoting agents andwherein the at least one bioactive agent comprises an antineoplasticagent and wherein the antineoplastic agent is selected from the groupconsisting of paclitaxel and 5-fluorouracil.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

An increasing geriatric population and associated health complicationsdue to compromised functionality of different urinogenital conduitsdirected the attention of contemporary investigators to exploretime-dependent corrective measures relying on the use of temporarydevices made of absorbable/biodegradable polymers which can beformulated to be disintegratable and radiographically detectable. Thisalso obviates the need for removal following the conclusion of theircorrective functions. Typical applications of this clinical strategywere the subject of recent patent applications on absorbable andabsorbable/disintegratable radiopaque endourological stents (U.S.application Ser. No. 11/346,117; 11/204,822; and 60/650,240). However,this prior art did not address patent-specific requirements, dependingon age, type of urinogenital conduits (e.g., urethra, ureter, vasdeferens, and fallopian tube), type of ailment and level of urgency andother factors, such as patient comfort during deployment of the device.Accordingly, this invention focuses on the use of (1) hydrophilicadditives, such as polyethylene glycol and its copolymers, as well asacylated derivatives thereof, with the matrix polymer, to improve thedevice surface lubricity and hence patient comfort during deployment;(2) radiochemical sterilization using 3 to 15 kGy of gamma radiation orE-beam to achieve reproducible sterility while controlling the radiationdose to modulate the absorption/disintegration and strength lossprofiles—the higher dose accelerates the rate of degradation andshortens the residence time at the biological site; (3) traditionalhigh-energy radiation sterilization in the presence of dry air ornitrogen environments to achieve reproducible sterility and also tomodulate the absorption/disintegration and strength loss profile byvarying the radiation dose between 25 and 40 kGy, with or withoutchanging the dose rate to accentuate the radiation effect (using gammaradiation or E-beam), particularly when the gas environment in thehermetically sealed package is dry air or nitrogen; and (4) a bioactiveactive agent, including triclosan, to reduce the incidence of infectionat the biological site. Accordingly, the teaching of the presentinvention entails the proper inventive steps to address theaforementioned points.

Further illustrations of the present invention are provided by thefollowing examples:

EXAMPLE 1 Synthesis and Characteristics of Radiopaque, Triaxial,Segmented Glycolide Copolymer (MG5-B) for Use in Coil Production

The reaction apparatus was comprised of a 1 L stainless steel kettlewith a 3-neck glass lid equipped with an overhead mechanical stirringunit, vacuum adapter, and nitrogen inlet. After obtaining a vacuum ≦0.5mmHg, the apparatus was purged with nitrogen. The polymeric initiator,paxTMC-1, is a polytrimethylene carbonate (TMC) initiated bytrimethylolpropane at a monomer to initiator ratio of 15. An initialcharge of paxTMC-1 (9.15 g), predried at 220° C. barium sulfatemicroparticles (245 g, diameter=1-4 μm), glycolide (313.8 g, 2.7048moles), and ε-caprolactone (132.1 g, 1.1592 moles) was added to thekettle. The apparatus was then lowered into an oil bath.

The apparatus and its contents were placed under vacuum at 40° C. for 1hour. The system was then purged with nitrogen. The temperature of theoil bath was increased to 95° C. and the contents mixed thoroughly. Oncemixed the final charge, a 0.2 M toluene solution of stannous octanoate(2.576 mL, 5.152×10⁻⁴ moles) was added. The temperature of the oil bathwas increased to 180° C. and mixing was continued as long as possible,then the reaction was maintained at 180° C. for 7 hours.

The polymer was frozen, removed and ground. The ground material wassieved. Polymer was transferred to a 2 L pear shaped glass flask andplaced on a Buchi rotavapor. After obtaining a vacuum of 0.25 mmHg, theflask was lowered into an oil bath. The temperature was increased to 40°C. After 2 hours at 40° C., the temperature of the oil bath wasincreased to 80° C. After 1 hour at 80° C., the temperature wasincreased to 110° C. Temperature was maintained at 110° C. for 4 hours.

The inorganic content was determined using ASTM ash test to be between38-40%. The inherent viscosity using Hexafluoroisopropanol as a solventwas about 0.95 dl/g. The melting temperature and heat of fusion, asdetermined by differential scanning calorimetry, were about 215° C. andabout 35 J/g, respectively.

EXAMPLE 2 Melt-Spinning and Properties of Radiopaque Monofilaments UsingMG5-B from Example 1 and Its Processing Into a Coiled Scaffold (CS)

A single screw extruder with four zones was used to extrude the polymerinto monofilament. The polymer from Example 1 was extruded using a 0.6mm die. A 325 line per inch filter pack was used. Zone 1 was maintainedat 100° C. Zone 2 was maintained at 175° C. Zone 3 was maintained at212° C. Zone 4/Spin Pack were maintained at 214° C. The metering pumpwas operated at 8 rpm while the take up roll was set at 40-60 rpm. Thecollected monofilament had diameters between 0.58 mm and 0.61 mm. Thefiber was drawn at 4.5× in the first stage at 55° C. and 0.5× in thesecond stage at 70° C. resulting in a diameter of 0.30 mm to 0.33 mm.The free shrinkage was 8.85% to 10.43% at 50° C. The fiber was relaxedone half the free shrinkage plus 2% at 70° C. The resulting fiber had amaximum load of about 13N and was dimensionally stable.

The processed radiopaque monofilament was then coiled in a helicalmanner onto a 0.55″ diameter Teflon cord which maintained the innerdiameter of the scaffold. The material was applied using a customdevice, placing 33 to 35 coils per inch.

EXAMPLE 3 Synthesis and Characterization of a Triaxial, SegmentedGlycolide Copolymer (MG-9) For Use in Preparing Knitted Scaffolds

The reaction apparatus was comprised of a 1 L stainless steel kettlewith a 3-neck glass lid equipped with an overhead mechanical stirringunit, vacuum adapter, and nitrogen inlet. After obtaining a vacuum of0.5 mmHg, the apparatus was purged with nitrogen. An initial charge ofpaxTMC-1 (16.0 g), as mentioned in Example 1, ε-caprolactone (38.6 g,0.3382 moles), and Glycolide (745.4 g, 6.4262 moles) was added to thekettle. The apparatus was then lowered into an oil bath.

The kettle and the contents are heated to 110° C. and mixed underpositive nitrogen pressure. Once the polymeric initiator appears to bethoroughly dissolved into the monomer, a 0.2 M toluene solution ofstannous octanoate (0.966 ml, 1.933×10⁻⁴ moles) was added. Thetemperature is increased to 180° C. Stirring is stopped when polymermixture gets viscous. The reaction is maintained at 180° C. for 5 hours.

The polymer was frozen, removed and ground. The ground material wassieved. Polymer was transferred to a 2 L pear shaped glass flask andplaced on a Buchi rotavapor. After obtaining a vacuum of 0.5 mmHg, theflask was lowered into an oil bath. The temperature was increased to 40°C. After 2 hours at 40° C., the temperature of the oil bath wasincreased to 80° C. After 1 hour at 80° C., the temperature wasincreased to 110° C. Temperature was maintained at 110° C. for 4 hours.

The inherent viscosity using Hexafluoroisopropanol as a solvent wasabout 1.3 dl/g. The melting temperature, as determined by differentialscanning calorimetry, was about 218° C.

EXAMPLE 4 Melt-spinning and Properties of Multifilament Yarn Using MG-9from Example 3 and Its Processing to a Knitted Scaffold (KS)

A single screw extruder with five zones was used to extrude the polymerinto multifilament. The polymer from Example 3 was extruded using a 20hole die with 0.018″ diameter holes. A 400 line per inch filter pack wasused. Zone 1 was maintained at 190° C. Zone 2 was maintained at 210° C.Zone 3 was maintained at 222° C. Zone 4/Pump was maintained at 228° C.Zone 5/Spin Pack were maintained at 228° C. The 0.584 cc/rev Zenithmetering pump was operated at 6.0 rpm while the denier control roll wasset to a linear speed of 315 meters/minute. The fiber was then orientedover three high speed godets traveling at 320, 465, 480 M/min. andheated to 60, 80, 26° C. respectively. The collected multifilament wasthen reoriented at speeds of 250 M/min to 280 M/min, and at atemperature of 100° C. The resulting fiber had a tenacity of 3.26 and adenier of 80.4.

The processed multifilament was then plied once to generate a 40filament fiber and then weft knitted using a lamb circular knitter ontothe coiled scaffold from Example 2 in a continuous manner. A ⅞″ knittingcylinder with 12 course gauge needles was used to form the knittedscaffold over the coiled scaffold.

EXAMPLE 5 Synthesis and Characterization of a Triaxial, Segmentedl-Lactide Copolymer (SVG-12) For Use as a Reinforced Composite Matrix(CM)

The reaction apparatus was comprised of a 4 L stainless steel reactorequipped with an overhead mechanical stirring unit, vacuum adapter, andnitrogen inlet. After obtaining a vacuum ≦0.5 mmHg, the apparatus waspurge with nitrogen. Oil is heated and circulated through the jacketedreactor to control the temperature. An initial charge of glycolide(254.9 g, 2.1976 moles), trimethylene carbonate (348.7 g, 3.4185 moles),predried triethanolamine (3.0319 g, 2.0348×10⁻² moles), stannousoctanoate (354.5 mg, 8.752×10⁻⁴ moles), and ε-caprolactone (974.3 g,8.5463 moles) was added a 2 L flask and dried under high vacuum for 1.25hours at 40° C. The flask was then added to the 4 L reactor.

The system was then purged with nitrogen. The temperature of the oil wasincreased to 175° C. and the contents mixed thoroughly for 6.5 hours andthen the temperature was reduced. Once mixed, the final charge, ofglycolide (226.6 g, 1.9534 moles) and l-Lactide (1195.5 g, 8.3021 moles)was added. The temperature of the oil was then increased to 135° C. andmaintained for 19 hours.

The polymer was then removed and dissolved at a concentration of 4milliliters per 1 gram in dichloromethane (DCM) so that the polymer canbe precipitated out in −60° C. isopropyl alcohol (IPA) and any monomerwill stay dissolved and be rinsed away. The polymer is then allowed todry to a constant weight.

The inherent viscosity using Chloroform as a solvent was about 1.4 dl/g.The melting temperature and heat of fusion, as determined bydifferential scanning calorimetry, were about 110° C. and about 7.2,respectively. The M_(n) and M_(w) were determined by GPC indichloromethane (M_(n)=85 kDa and M_(w)=146 kDa).

EXAMPLE 6 Assembling a Typical Composite Ureteral Stent Construct

Preparation of polymer matrix solution—A polymer solution containingSVG-12 from Example 5, polyethylene glycol (M_(W)=4600) and acetone wasprepared by addition of 1600 milliliters of acetone to one 64-ounce jar,followed by addition of 16.0 grams of PEG 4600 and 144.0 grams ofpurified SVG-12. The solution was enclosed and brief heating was used tofacilitate dissolution. The jar was placed on automatic rollingapparatus until complete dissolution was reached.

Continuous impregnating of knitted core—The dry, knitted core wasimpregnated with a polymer matrix of SVG-12 and PEG 4600 using acontinuous matrix-impregnating process that involved the continuousmovement of the knitted core material through a 0.75-liter bath ofpolymer solution. The knitted core was unspooled from the beginning ofthe impregnating apparatus and immediately fed into the bath of polymersolution, where two in-line submerged pulleys kept the scaffold materialsubmerged for the length of the bath. As the impregnated material exitedthe bath, it was passed through an air-circulating drying tube heated to40° C., then a stainless-steel element heated to 50° C., and then theimpregnated material was spooling onto a final take-up spool.

Shape-forming of impregnated, knitted core—The impregnated material waswrapped onto custom-built racks equipped with two parallel stainlesssteel bars of 0.5 inch diameter, which could be adjusted for separationdistance to control final stent length. The newly-impregnated, knittedcore was wrapped onto these racks in a continuous fashion. The rackswere annealed at 130° C. for 30 minutes, and then the racks were allowedto cool to room temperature in a laminar flow hood. Multiple stents wereremoved from each rack by cutting the scaffolding material atappropriate positions along interior positions of the separation rods ofthe shape-forming racks. These stents, which still contained a Tefloncore, were modified by addition of a UVJ marker to each stent stemwithin one centimeter of what would ultimately become the proximal loopof each stent. Then, the proximal loops of all stents were given anadditional coating by hand-dipping each proximal loop into 150milliliters of a 10% (w/v; 9.3% SVG-12, 0.7% PEG 4600) polymer solutionof SVG-12 and PEG 4600 in acetone. Stents were hung by distal loops in alaminar flow hood to dry. Then, Teflon cores were removed from eachstent by securing one end of the Teflon to position-fixed vise-grippliers as the opposite end of the Teflon was stretched using a secondset of vise-grip pliers. A clean cut was made in the stretched Tefloncore at the secured end, and then the Teflon core of reduced diameterwas pulled through the stent and discarded. Finally, each stent wastrimmed to the appropriate specifications.

EXAMPLE 7 Package Design and Packaging of UST from Example 6

The UST, as described in Example 6, is packaged in a tray that was madeof a polyester suitable for use in radiation sterilization. A liner thatfits in the tray has tabs that retain the stent in location. The trayhas a top and bottom section with closure devices on both ends andprovided protection to the stent during shipping and storage. The trayis also placed in a foil pouch, which provided moisture barrier, toprotect the UST.

EXAMPLE 8 Radiation Sterilization of UST from Example 6 and Evaluationof the Sterile Device Properties

Sterilization of the UST from Example 6, package as described in Example7 was conducted using 25 KGy of gamma radiation.

The melting temperature, as determined by differential scanningcalorimetry, were 52-62, 114-144, 198-208, and 206-216° C.,respectively. The functionality of the stent was determined throughmechanical testing. This entails: (1) determining the axial compression(to ensure the stent is insertable with traditional placementtechniques) which was found to be about 4N; (2) determining the radialcompression for a 1″ section of the stent which was found to be about94N; (3) measuring the curl retention which was found to be about 0.5N;and (4) measuring the total yield strength of the stent which revealed avalue of about 93N. Mass loss after one week in vitro at pH 7.2 and 37°C. was found to be 3.3% for the non-sterilized stent and 6.3% for theGamma sterilized stent.

EXAMPLE 9 Preparation and Properties of an Antimicrobial EndoureteralStent (A-UST)

Preparation of a polymer matrix solution of Example 6 was adjusted toinclude triclosan at a concentration of 0.5% or 1% of the solid polymerweight. Antimicrobial susceptibility testing demonstrated that theUriprene stent provided a sustained drug release and displayed asignificant inhibitory effect on S. aureus for at least 8 days.

1. A multi-component absorbable/disintegratable, fiber-reinforced,radiopaque composite, non-migrating stent for a urinogenital conduit,the stent comprising a first component comprising an absorbable, highlycompliant, hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, the coil shroudedwith a knitted mesh construction comprising an absorbable multifilamentyarn, wherein the stent exhibits a one- to ten-week, radiomodulatedabsorption/disintegration and strength retention profiles.
 2. Amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit as set forthin claim 1 wherein the urinogenital conduit is selected from the groupconsisting of ureters, urethras, vas deferens, uterine tubes, fallopiantubes and ejaculatory ducts.
 3. A multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit as set forth in claim 1wherein the stent is in the form of a tube having a main central bodyand at least one position-retaining end comprising a flexible extensionof the main central body, and having a loop shape with an open endparallel to the axis of the main central body after insertion in theurinogenital conduit wherein the loop can be made co-linear with the aidof an applicator.
 4. A multi-component absorbable/disintegratable,fiber-reinforced, radiopaque composite, non-migrating stent for aurinogenital conduit as set forth in claim 3 in the form of anendoureteral stent having a diameter that is less than that of theurinogenital conduit.
 5. A multi-component absorbable/disintegratable,fiber-reinforced, radiopaque composite, non-migrating stent for aurinogenital conduit as set forth in claim 4 wherein the matrixcomprises an absorbable, high molecular weight, low-crystallinity,segmented polyaxial copolyester exhibiting an inherent viscosity of fromabout 0.5 to about 2.0 dL/g and heat of fusion (ΔH_(f)) of from about 2to about 30 J/g and derived from l-lactide and at least one additionalmonomer selected from the group consisting of glycolide, trimethylenecarbonate, ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-one and amorpholinedione.
 6. A multi-component absorbable/disintegratable,fiber-reinforced, radiopaque composite, non-migrating stent for aurinogenital conduit as set forth in claim 1 wherein the matrixcomprises an absorbable, segmented, polyaxial copolyester and a highmolecular weight, hydrophilic polymeric additive having a molecularweight of about 1 to about 70 kDa, the additive selected from the groupconsisting of polyethylene glycol, and polyethylene glycol end-graftedwith at least one monomer selected from the group consisting ofl-lactide, glycolide, trimethylene carbonate, ε-caprolactone,p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione.
 7. Amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit as set forthin claim 1 wherein the matrix comprises an absorbable polyether-estercomprising an aliphatic polyether glycol end-grafted with at least onemonomer selected from the group consisting of l-lactide, glycolide,trimethylene carbonate, ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-oneand a morpholinedione and having an inherent viscosity of from about 0.6to about 1.8 dL/g and an overall heat of fusion (ΔH_(f)) of from about 5to about 30 J/g.
 8. A multi-component absorbable/disintegratable,fiber-reinforced, radiopaque composite, non-migrating stent for aurinogenital conduit as in claim 1 wherein the load-bearing radiopaquecentral reinforcing coil comprises a hybrid monofilament consisting offrom about 30 to about 60 weight percent of barium sulfatemicroparticles dispersed in a crystalline high molecular segmentedpolyaxial copolyester exhibiting an inherent viscosity of from about 0.6to about 2.0 dL/g and a heat of fusion (ΔH_(f)) of from about 20 toabout 80 J/g, the copolyester derived from glycolide and at least oneadditional monomer selected from the group consisting of l-lactide,trimethylene carbonate, ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-oneand a morpholinedione.
 9. A multi-component absorbable/disintegratable,fiber-reinforced, radiopaque composite, non-migrating stent for aurinogenital conduit as set forth in claim 1 wherein the absorbablemultifilament yarn of the knitted mesh comprises a crystalline, highmolecular weight segmented polyaxial copolyester exhibiting an inherentviscosity of from about 0.6 to about 2.3 dL/g and a heat of fusion(ΔH_(f)) of from about 30 to about 90 J/g, the copolyester derived fromglycolide and at least one additional cyclic monomer of l-lactide,trimethylene carbonate, ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-oneand a morpholinedione.
 10. A multi-component absorbable/disintegratable,fiber-reinforced, radiopaque composite, non-migrating stent for aurinogenital conduit as set forth in claim 1 wherein the stent ispackaged in a dry, hermetically sealed foil pack and is irradiated withfrom about 3 to about 35 kGy of high energy radiation.
 11. Amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit as set forthin claim 1 wherein the stent is packaged in a dry, hermetically sealedfoil pack and is irradiated with from about 30 to about 40 kGy of gammarays or electron beam radiation.
 12. A multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit as in claim 1 wherein thestent is packaged in a dry, hermetically sealed foil pack containing aformaldehyde-generating packet, and is irradiated with from about 3 toabout 15 kGy of gamma rays or electron beam radiation.
 13. Amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit, the stentcomprising a first component comprising an absorbable, highly compliant,hydrowettable, tubular matrix, the matrix reinforced with aload-bearing, radiopaque central coil, the coil comprising an absorbablepolyester/inorganic radiopaque hybrid composition, at least threeabsorbable strands overlying the coil and extending along thelongitudinal axis of the stent, the strands comprising a copolyesterderived from at least one monomer selected from the group consisting ofl-lactide, glycolide, trimethylene carbonate, ε-caprolactone,p-dioxanone, 1,5-dioxepan-2-one and a morpholinedione, wherein the stentexhibits a one- to ten-week, radiomodulated absorption/disintegrationand strength retention profiles.
 14. A multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit as set forth in claim 13wherein the absorbable strands are selected from the group consisting ofmonofilament yarn having a diameter between about 20 and about 150microns, a 20-filament, 60 to 100 denier yarn, and a braidedmultifilament yarn having a diameter of from about 0.02 to about 0.2 mm.15. A multi-component absorbable/disintegratable, fiber-reinforced,radiopaque composite, non-migrating stent for a urinogenital conduit asset forth in claim 1 further comprising at least one bioactive agentselected from the group consisting of antimicrobial, antiviral,antineoplastic, anti-anesthetic, anti-inflammatory, analgesic, andcell-growth promoting agents.
 16. A multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit as in claim 15 whereinthe at least one bioactive agent comprises an antimicrobial agent andwherein the antimicrobial agent comprises an antibacterial agentselected from the group consisting of triclosan, clindamycin, mitomycin,doxycycline, and metronidazole.
 17. A multi-componentabsorbable/disintegratable, fiber-reinforced, radiopaque composite,non-migrating stent for a urinogenital conduit as in claim 15 whereinthe at least one bioactive agent comprises an antimicrobial agent andwherein the antimicrobial agent comprises antifungal agent selected fromthe group consisting of miconazole, fluconazole, and ketoconazole.
 18. Amulti-component absorbable/disintegratable, fiber-reinforced, radiopaquecomposite, non-migrating stent for a urinogenital conduit as set forthin claim 15 wherein the at least one bioactive agent comprises anantineoplastic agent and wherein the antineoplastic agent is selectedfrom the group consisting of paclitaxel and 5-fluorouracil.